CURRENT VIEWS ON THE MECHANISMS OF RESISTANCE TO QUINOLINE-CONTAININGDRUGS IN PLASMODIUM-FALCIPARUM

The issue of chloroquine resistance in Plasmodium falciparum and cross -resistance patterns with other related chemotherapeutic agents has be en the subject of intense interest for many years. Despite this level of investigation, the picture remains very unclear, Although it is acc epted that chloroquine resistance is, at least in part, a function of reduced drug accumulation, the question of reduced drug uptake versus enhanced efflux is yet to be resolved at both the molecular and bioche mical levels. Further, the absolute cross-resistance patterns of chlor oquine-resistant isolates to closely related analogues is a matter for debate, although there appears to be a reciprocal arrangement between resistance to chloroquine and resistance to mefloquine, halofantrine and possibly quinine. Evidence is presented for the coexistence of two or more chloroquine-resistance mechanisms in isolates of P. falciparu m, only one of which is verapamil sensitive. In addition, an analysis of cross-resistance patterns, as measured by the inoculum effect, is p resented.